Mechanism of Action of Choleragen and the Glycopeptide Hormones: Is the Nicotinamide Adenine Dinucleotide Glycohydrolase Activity Observed in Purified Hormone Preparations Intrinsic to the Hormone?*

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Abstract
Choleragen and the glycopeptide hormones are thought to exert their effects on cells through activation of adenylate cyclase. The catalytic subunit of choleragen possesses both NAD glycohydrolase and ADP-ribosyltransferase activities. Since the glycopeptide hormones share with choleragen certain homologies of structure (Ledley et al, Biochem. Biophys. Res. Commun.69: 852, 1976), we investigated whether these hormones might catalyze a NAD glycohydrolase reaction. NAD was required for activation of bovine thyroid particulate adenylate cyclase by choleragen, but not by bovine TSH. Highly purified preparations of human CG (hCG) and bovine TSH possessed NAD glycohydrolase activity. This activity was present in apparently homogeneous preparations of the α and β subunits of hCG and in the asialo or reduced carboxymethylated derivatives. Recombination of the hCG subunits, which restores biological potency, did not, however, produce enhancement of NAD glycohydrolase activity. Furthermore, this activity did not cochromatograph with purified preparations of hCG or its α and β subunits on Sephadex G-100. It appears, therefore, that the NAD glycohydrolase activity is not an intrinsic property of hCG or its subunits. Thus, there is no evidence that these glycopeptide hormones activate adenylate cyclase through an NAD-dependent mechanism analogous to that of choleragen. (Endocrinology102: 415, 1978)